Anti-infective therapy Flashcards
how do bacteria become resistant to antibiotics
acquiring mutations that counteracts antibiotics by doing the following:
- degradation/modification of antibiotic (beta lactamases)
- reduction in the bacterial antibiotic concentration (interference with entry [lipid coat/loss of porins from which antibiotics enter/ creation of efflux pumps])
- modification of antibiotic target(alteration in cell wall precursor/ changes in target enzymes[penicillin binding protein]/alteration in ribosomal binding site)
how can the continued selection of highly resistant organisms be prevented
administer a high dose (high AUC/MIC ration [area under curve/mean inhibitory concentration) because the more rapid the selective pressure on the bacteria the less likely the selection for a highly resistant traits
short course of antibiotic (<5days )
what are the strategies that underline optimal antibiotic usage
administer a high dose (high AUC/MIC ration [area under curve/mean inhibitory concentration)
short course of antibiotic (<5days )
how do bacteria transfer antibiotic traits
those bacteria confer antibiotic resistance to others by:
conjugation (plasmid transferred)
transduction (DNA is injected from a phage)
transformation (DNA is donated to another bacteria)
what is the mean inhibitory concentraion
the least amount of antibiotic needed to prevent visible growth of a bacterium
the amount administered should be just above the MIC for half of the duration of treatment
steps for antibiotic regimen
know if its a bacteria infection (WBC count mainly neutrophils [viral increases lymphocytes] or procalcitonin can differentiate better)
locate the site of infection
take into consideration nosocomial infections/previous antibiotic use
switch to narrow-spectrum antibiotic within 3 days
steps for antibiotic regimen
know if its a bacteria infection (WBC count mainly neutrophils [viral increases lymphocytes] or procalcitonin can differentiate better)
locate the site of infection
take into consideration nosocomial infections/previous antibiotic use
take into consideration the patents status (immunity, hepatic function , age, severity of illness)
switch to narrow-spectrum antibiotic within 3 days
when do you switch antibiotics
in the case of a new infection/superinfection
superinfection indications
new fever
increased peripheral WBC
increased inflammatory exudate at the site of injection (sign for catheter associated infection)
increased polymorphonuclear lymphocytes on gram stain
name beta lactam antibiotics and their MOA and toxicity
penicillin, cephalosporins, carbapenems
MOA: B lactam rings binds to penicillin binding proteins that’s important for bacterial cell wall cross-linking
since they require active division of bacteria they are all antagonized by bacteriostatic antibiotics
all peneillins have short half life
toxicity:
hypersensitivity= anaphylaxis
nephrotoxicity (aminoglycosides with cephalosporins)
increased prothrombin time (cephalosporines interfere with Vit K)
encephalopathy in the elderly (cefepime)
ceftriaxone is secreted in the blie and can cause cholecystitis
seizures in patients with renal dysfunction
indications for penicillins and their dosing
S. pyogenes
S. viridans
Neiserria menengiditis
s. pneumoniae
IM/IV with a short half life, excreted by the kidneys, narrow spectrum
what’s the difference between aminopenicillins and penicillin’s
aminopenicillins are modified penicillins that can survive stomach acidity thus can be given orally
ampicillin plus aminoglycoside is treatment of choice for enterococci
amoxicillin-clavulanate are for H. influenzae staphylococcus
what are penicillinase resistant penicilins and their indication
Nafcillin and oxacillin
modified so it is resistant to penicillinase produced by penicillin resistant strains
it has hepatic clearance so dose doesn’t have to be adjusted in renal dysfunction
primarily used for methicillin sensitive staph aureus and cellulitis
name the usage of different types of cephalosporines (different generations)
ALL generations inhibit cell wall synthesis/bactericidal
1st gen: G positive cocci, for surgical prophylaxes, Cant cross BBB
2nd gen: aerobic/anaerobic G negative bacilli, vit k deficiency, (decreases prothrombin time )
3rd gen: G negative bacilli H. influenza/N. gonorrhea / N. menegiditis. for community acquired pneumonia and meningitis
4th gen: broad spectrum, pseudomonas and S. aureus and nosocomial infections
5th gen: MSSA/MRSA and penicillin resistant S. pneumoniae. penetrates all tissue (BBB as well). good for community acquired pneumonia
adverse reactions of cephalosporines
hypersensitivity reactions autoimmune hemolytic anemia disulfiram like reaction vit k deficiency nephrotoxic synergy with aminoglycosides
Cephalosporine mnemonic
1st gen: az ale cefAZolin, cefALExin
2nd gen: process of elimination
3rd: 3T’s cefTRIaxone, cefTAXime, cefTAZidime
4th gen:4 cefourpime or Cefepime
5th: cefSTARoline or ceftaroline. star has 5 arms
from a YouTube video, don’t blame me on how bad that is
carbapenems, structure, usages and side effects
member of beta lactams
for high risk infections and suspected multi drug resistant bacteria
modified B lactam ring that’s highly resistant to cleavage (resistance to beta lactamase)
it penetrates all tissue
people who are allergic to penicillin might be allergic to carbapenems
used most G positive
G negative include listeria and nocardia
usage for suspected mixed aerobic and anaerobic (sepsis, pyelonephritis, meningitis)and nosocomial infection
Side effects: cause seizures in high doses, dramatically changes normal flora
aminoglycosides MOA
have a positive charge that is activated by beta lactamas (thus don’t use with beta lactam antibiotics)
they inhibit protein synthesis
toxicity of aminoglycosides
low therapeutic index compared to toxicity
ototoxicity: neomycin has the highest risk of toxicity
nephrotoxicity:
damage to proximal tubes, reversible
significant reduction in GFR
higher incidence in the elderly
dosing of aminoglycosides
once a day to reduce (but not eliminate) nephrotoxicity but not recommended for enterococcal endocarditis
good for gram negative bacteria
require active bacterial growth
affect starts after 2 hours
MOA of glycopeptides and name some
binds a cell wall precures that’s different to the b lactam antibiotics and messes the permeability
also affects RNA synthesis
require active bacterial growth (don’t use bacteriostatic)
vancomycin is an example
vancomycin toxicity
rapid infusion leads to red man syndrome (flushing of the upper body) which is prevented by a 1hour long infusion
phlebitis is common (vein inflammation)
ototoxicity is preceded by tennitus, so stop when tinnitus presents
what do you use vancomycin for
MRSA penicillin resistant S. pneumoniae coagulase negative staphylococci penicillin allergic S. pyogenes excellent against enterococcus but vancomycin resistant enterococci are emerging
indications
sepsis Coagulase negative staphylococcal
endocarditis
pneumococcal meningitis S. pneumonia
macrolides and ketolides MOA and side effects
same mechanism that inhibits RNA dependent protein synthesis by blocking protein exit from ribosome by binding to 50s
bacteriostatic/ bactericidal
SE:
GI irritation with erythromycin is the major toxicity
hypersensitivity reactions
exacerbations of myasthenia gravis
indications for macrolides
Gram positive community acquired pneumonia legionella pneumophilia mycoplasma helicobacter pylori mycobacterium avium intercellulare!! (clarithromycin )
